The invention relates to novel strains of lactic ferments and to their use for the production of foods endowed with anxiolitic properties.
Stress, which is a defensive reaction of the body against external attacks, causes in particular at the level of the nervous system, biological disruptions which can develop into various pathological conditions. The latter can manifest themselves directly at the psychological level, in particular in the form of anxiety, and/or can take the form of somatic manifestations, such as high blood pressure, gastric ulcerations and the like. They frequently progress to chronic states.
To treat the consequences of stress, whether involving anxiety or somatic manifestations, anxiolytic, and in particular benzodiazepines, are frequently used. However, these medicaments, which can rapidly cause a phenomenon of addiction, may not be suitable for a long-term treatment. Moreover, their anxiolytic action is accompanied in particular by sedative properties which can cause unwanted side effects.
Some research studies have demonstrated the existence, in milk or in products derived therefrom, of substances endowed with pharmacological properties toward pathological conditions linked to stress. In particular, PCT application WO 98/05343, in the names of CALPIS CO. AND GROUPE DANONE, describes an agent possessing antistress properties manifested by an antihypertensive effect. This agent is obtained by fermenting milk with a lactic acid bacterium of the genus Lactobacillus, in particular Lactobacillus helveticus. It is resistant to sterilization and can be used to prepare foods participating in the prevention and/or treatment of the peripheral (somatic) effects of stress, and which can be consumed in the context of the usual diet, regularly and over long periods. No central, in particular anxiolytic, effect resulting from the administration of this agent is demonstrated in PCT application WO 98/05343.
Application EP 95402697 in the name of: SOCIETE COOPERATIVE LAITIERE AGRICOLE D""ARTOIS ET DES FLANDRES, LA PROSPERITE FERMIERE, describes a decapeptide resulting from the tryptic hydrolysis of casein csl. The parental administration of this decapeptide, or of the tryptic hydrolysate comprising it induces an anxiolytic and anticonvulsant effect of the same type as that by the benzodiazepines. On the other hand, this document provides no information relating to the activity of this hydrolysate when administered orally, and the possibility of incorporating it into foods in order to confer antistress properties on them.
The inventors have now demonstrated, in dairy products fermented by certain strains of lactic acid bacteria, the existence of one or more active ingredients capable of inducing, when they are administered orally, an anxiolytic-type antistress effect, without possessing the sedative properties of the benzodiazepines.
The subject of the present invention is also the use of at least one of the newly isolated and characterized strains of lactic acid bacteria mentioned above, for the production of a nonsedative anxiolytic.
The subject of the present invention is a strain of lactic acid bacterium chosen from the group consisting of:
the Streptococcus thermophilus S242 strain deposited on Feb. 24, 1999 in accordance with the Budapest Treaty at the CNCM (Collection Nationale de Cultures de Micro-organismes), 28 rue du Docteur Roux, 75724 Paris, under the number I-2130;
the Streptococcus thermophilus S003 strain deposited on 24 February 1999 in accordance with the Budapest Treaty at the CNCM (Collection Nationale de Cultures de Micro-organismes), 28 rue du Docteur Roux, 75724 Paris, under the number I-2129;
the Lactobacillus gasseri L012 strain deposited on Feb. 24, 1999 in, accordance with the Budapest Treaty at the. :-CNCM (Collection Nationale de Cultures de Micro-organismes), 28 rue du Docteur Roux, 75724 Paris, under the number I-2131;
the Lactobacillus acidophilus L030 strain deposited on Feb. 24, 1999 in accordance with the Budapest Treaty at the CNCM (Collection Nationale de Cultures de Micro-organismes), 28 rue du Docteur Roux, 75724 Paris, under the number I-2132.
The subject of the present invention is also the newly isolated and characterized strains of lactic acid bacteria mentioned above, which can be used for the production of a nonsedative anxiolytic.
The characteristics of the strains of lactic acid bacteria in accordance with the invention are summarized in tables I and II below.
The present invention relates in particular to the use, for the production of a nonsedative anxiolytic, of at least one Streptococcus thermophilus strain chosen from the S242 strain and the S003 strain, combined with the S. thermophilus S147 strain deposited at the CNCM on Dec. 30, 1994 under the number I-1520.
The present invention also relates to lactic ferments comprising at least one strain in accordance with the invention, advantageously combined with another strain of lactic acid bacterium.
According to a preferred embodiment of a lactic ferment in accordance with the invention, it comprises at least the S. thermophilus S242 strain and/or the S. thermophilus S003 strain, advantageously combined with the S. thermophilus S147 strain.
The subject of the present invention is also a non-sedative anxiolytic comprising at least one strain of lactic acid bacterium in accordance with the invention as defined above, or capable of being obtained from a culture of said strain.
For the production of a nonsedative anxiolytic in accordance with the invention, at least one strain of lactic acid bacterium in accordance with the invention is cultured; in particular a lactic ferment comprising at least the S. thermophilus S424 strain and/or the S. thermophilus S003 strain advantageously combined with the S. thermophilus S147 strain, and optionally with the L. gasseri L012 strain and/or the L. acidophilus L030 strain, is cultured in an appropriate medium, that is to say a medium comprising at least one substrate allowing the growth of said bacteria. Said culture medium is preferably milk or a milk-based medium. It may be chosen in particular from the milks of the various species of mammals, optionally semiskimmed or skimmed, the products resulting from the dilution or the concentration of these milks, such as for example ultrafiltration of diafiltration retentates, milk-based media, such as for example bases for milk-based foods, bases for yogurt and the like. These milks may, in addition, be supplemented with, for example, lactose, minerals, vitamins, fatty substances or otherwise, hydrophilic milk solids, soybean proteins, plant extracts and the like.
This medium is inoculated with a culture comprising at least one strain of lactic acid bacterium in accordance with the invention, preferably comprising 107 to 109 bacteria/ml. The optimum culture conditions vary according to the strain or the mixture of strains involved. For example, if the culture for inoculation consists of a strain or a mixture of strains of Streptococcus thermophilus, the culture will be carried out for about 24 h and the optimum culture temperature will be between 30 and 44xc2x0 C.; if the culture for inoculation consists of a strain or a mixture of strains of L. acidophilus or of L. gasseri, the culture will be carried out for about 16 h and the optimum culture temperature will be between 37 and 44xc2x0 C. In the case where the culture for inoculation combines at least one Streptococcus thermophilus strain with at least one L. acidophilus or L. gasseri strain, the culture will be carried out for 16 to 24 h, and the optimum culture temperature will be between 37 and 44xc2x0 C.
The bacterial culture thus obtained possesses the properties of a nonsedative anxiolytic in accordance with the invention.
The nonsedative anxiolytics in accordance with the invention are active when administered orally. Regular administration thereof causes, after a few days, a reduction in anxiety, with no reduction in activity; it can be extended for a very long period, with no addiction effect, and without the appearance of unfavorable side effects. These properties, as well as the fact that it is possible to obtain them from micro-organisms belonging to species commonly used in the food industry, and from raw materials which are also intended for dietary use, make it possible to use them in the context of the manufacture of foods or dietary supplements, whose consumption exerts a beneficial effect in the context of the treatment or of the prevention of stress-related pathological states.
The subject of the present invention is also the food products or dietary supplements comprising a non-sedative anxiolytic in accordance with the invention.
These food products may be in particular products comprising at least one strain of lactic acid bacterium or a lactic ferment in accordance with the invention. They are in particular products which can be obtained by fermenting milk or a milk-based medium with said strain of said ferment. Food products in accordance with the invention can also be prepared by adding to any food which is fermented or otherwise a preparation comprising a nonsedative anxiolytic in accordance with the invention.
The beneficial effects of the foods in accordance with the invention generally appear starting from a dose of 5 ml/day/kg of weight, in the case of a fermented milk containing a total population (which may consist of one or more strains of bacteria in accordance with the invention) of lactic acid bacteria in accordance with the invention of at least 105 CFU/ml. Substantially higher doses can however be taken, with no harmful side effects.